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Journal articles on the topic 'MMV Malaria Box'

Author: Grafiati

Published: 14 March 2023

Last updated: 31 July 2025

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1

Müller, Joachim, Pablo A. Winzer, Kirandeep Samby, and Andrew Hemphill. "In Vitro Activities of MMV Malaria Box Compounds against the Apicomplexan Parasite Neospora caninum, the Causative Agent of Neosporosis in Animals." Molecules 25, no. 6 (2020): 1460. http://dx.doi.org/10.3390/molecules25061460.

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(1) Background: Neospora caninum is a major cause of abortion in cattle and represents a veterinary health problem of great economic significance. In order to identify novel chemotherapeutic agents for the treatment of neosporosis, the Medicines for Malaria Venture (MMV) Malaria Box, a unique collection of anti-malarial compounds, were screened against N. caninum tachyzoites, and the most efficient compounds were characterized in more detail. (2) Methods: A N. caninum beta-galactosidase reporter strain grown in human foreskin fibroblasts was treated with 390 compounds from the MMV Malaria Box.

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Allman, Erik L., Heather J. Painter, Jasmeet Samra, Manuela Carrasquilla, and Manuel Llinás. "Metabolomic Profiling of the Malaria Box Reveals Antimalarial Target Pathways." Antimicrobial Agents and Chemotherapy 60, no. 11 (2016): 6635–49. http://dx.doi.org/10.1128/aac.01224-16.

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ABSTRACTThe threat of widespread drug resistance to frontline antimalarials has renewed the urgency for identifying inexpensive chemotherapeutic compounds that are effective againstPlasmodium falciparum, the parasite species responsible for the greatest number of malaria-related deaths worldwide. To aid in the fight against malaria, a recent extensive screening campaign has generated thousands of lead compounds with low micromolar activity against blood stage parasites. A subset of these leads has been compiled by the Medicines for Malaria Venture (MMV) into a collection of structurally divers

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Fong, Kim Y., Rebecca D. Sandlin та David W. Wright. "Identification of β-hematin inhibitors in the MMV Malaria Box". International Journal for Parasitology: Drugs and Drug Resistance 5, № 3 (2015): 84–91. http://dx.doi.org/10.1016/j.ijpddr.2015.05.003.

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Wu, Wesley, Zachary Herrera, Danny Ebert, et al. "A Chemical Rescue Screen Identifies a Plasmodium falciparum Apicoplast Inhibitor Targeting MEP Isoprenoid Precursor Biosynthesis." Antimicrobial Agents and Chemotherapy 59, no. 1 (2014): 356–64. http://dx.doi.org/10.1128/aac.03342-14.

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ABSTRACTThe apicoplast is an essential plastid organelle found inPlasmodiumparasites which contains several clinically validated antimalarial-drug targets. A chemical rescue screen identified MMV-08138 from the “Malaria Box” library of growth-inhibitory antimalarial compounds as having specific activity against the apicoplast. MMV-08138 inhibition of blood-stagePlasmodium falciparumgrowth is stereospecific and potent, with the most active diastereomer demonstrating a 50% effective concentration (EC50) of 110 nM. Whole-genome sequencing of 3 drug-resistant parasite populations from two independ

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López-Arencibia, Atteneri, Ines Sifaoui, María Reyes-Batlle, et al. "Discovery of New Chemical Tools against Leishmania amazonensis via the MMV Pathogen Box." Pharmaceuticals 14, no. 12 (2021): 1219. http://dx.doi.org/10.3390/ph14121219.

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The protozoan parasite Leishmania causes a spectrum of diseases and there are over 1 million infections each year. Current treatments are toxic, expensive, and difficult to administer, and resistance to them is emerging. In this study, we screened the antileishmanial activity of the Pathogen Box compounds from the Medicine for Malaria Venture against Leishmania amazonensis, and compared their structures and cytotoxicity. The compounds MMV676388 (3), MMV690103 (5), MMV022029 (7), MMV022478 (9) and MMV021013 (10) exerted a significant dose-dependent inhibition effect on the proliferation of L. a

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Mann, Lea, Markus Lang, Philipp Schulze та ін. "Racemization-free synthesis of Nα-2-thiophenoyl-phenylalanine-2-morpholinoanilide enantiomers and their antimycobacterial activity". Amino Acids 53, № 8 (2021): 1187–96. http://dx.doi.org/10.1007/s00726-021-03044-1.

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AbstractNα-2-thiophenoyl-d-phenylalanine-2-morpholinoanilide (MMV688845, IUPAC: N-(1-((2-morpholinophenyl)amino)-1-oxo-3-phenylpropan-2-yl)thiophene-2-carboxamide) from the Pathogen Box® library (Medicines for Malaria Ventures, MMV) is a promising lead compound for antimycobacterial drug development. Two straightforward synthetic routes to the title compound starting from phenylalanine or its Boc-protected derivative are reported. Employing Boc-phenylalanine as starting material and the T3P® and PyBOP® amide coupling reagents enables racemization-free synthesis, avoiding the need for subsequen

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Alemán Resto, Yesmalie, and José A. Fernández Robledo. "Identification of MMV Malaria Box Inhibitors of Perkinsus marinus Using an ATP-Based Bioluminescence Assay." PLoS ONE 9, no. 10 (2014): e111051. http://dx.doi.org/10.1371/journal.pone.0111051.

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Ruecker, A., D. K. Mathias, U. Straschil, et al. "A Male and Female Gametocyte Functional Viability Assay To Identify Biologically Relevant Malaria Transmission-Blocking Drugs." Antimicrobial Agents and Chemotherapy 58, no. 12 (2014): 7292–302. http://dx.doi.org/10.1128/aac.03666-14.

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ABSTRACTMalaria elimination will require interventions that prevent parasite transmission from the human host to the mosquito. Experimentally, this is usually determined by the expensive and laboriousPlasmodium falciparumstandard membrane feeding assay (PfSMFA), which has limited utility for high-throughput drug screening. In response, we developed theP. falciparumdual gamete formation assay (PfDGFA), which faithfully simulates the initial stages of the PfSMFAin vitro. It utilizes a dual readout that individually and simultaneously reports on the functional viability of male and female mature

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Boyom, Fabrice F., Patrick V. T. Fokou, Lauve R. Y. Tchokouaha, et al. "Repurposing the Open Access Malaria Box To Discover Potent Inhibitors of Toxoplasma gondii and Entamoeba histolytica." Antimicrobial Agents and Chemotherapy 58, no. 10 (2014): 5848–54. http://dx.doi.org/10.1128/aac.02541-14.

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ABSTRACTToxoplasmosis and amebiasis are important public health concerns worldwide. The drugs currently available to control these diseases have proven limitations. Therefore, innovative approaches should be adopted to identify and develop new leads from novel scaffolds exhibiting novel modes of action. In this paper, we describe results from the screening of compounds in the Medicines for Malaria Venture (MMV) open access Malaria Box in a search for new anti-Toxoplasmaand anti-Entamoebaagents. Standardin vitrophenotypic screening procedures were adopted to assess their biological activities.

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Hostettler, Isabel, Joachim Müller, and Andrew Hemphill. "In VitroScreening of the Open-Source Medicines for Malaria Venture Malaria Box Reveals Novel Compounds with Profound Activities against Theileria annulata Schizonts." Antimicrobial Agents and Chemotherapy 60, no. 6 (2016): 3301–8. http://dx.doi.org/10.1128/aac.02801-15.

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Intracellular schizonts of the apicomplexansTheileria annulataandTheileria parvaimmortalize bovine leukocytes and thereby cause fatal diseases. The hydroxynaphthoquinone buparvaquone is currently the only option for the treatment of theileriosis, and resistance development has been reported. It is therefore tempting to investigate the repurposing of compounds effective against related apicomplexan parasites, such asPlasmodium. Here, we present the results of a screen of 400 compounds included in the open-access Medicines for Malaria Venture (MMV) malaria box on TaC12 cells, a macrophage-derive

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Kenneth Obiakor, Onyeka Chinwuba Obidiegwu, Keziah Uchechi Ajah, Christian Chidebe, Ajuzie Henry Ogechi, and Ikemefuna Chijioke Uzochukwu. "Discovery of antiadhesins of Helicobacter pylori from existing drugs and medicines for malaria ventures pathogen box compounds." GSC Biological and Pharmaceutical Sciences 20, no. 3 (2022): 198–212. http://dx.doi.org/10.30574/gscbps.2022.20.3.0356.

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Background: Helicobacter pylori infection is a worldwide problem with more than half of the world's population in both developed and developing countries are infected with this organism. The best-characterized H. pylori adhesins, Blood group antigen binding Adhesin (BabA) and Sialic acid binding Adhesin (SabA) are virulent factors which facilitate adhesion of the bacteria to the host cells. Methods: We determined the binding affinities of selected existing drugs and medicines for malaria venture pathogen box compounds to H. pylori adhesin receptors by molecular docking simulations. The 3D crys

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Bethencourt-Estrella, Carlos J., Atteneri López-Arencibia, Jacob Lorenzo-Morales, and José E. Piñero. "Repurposing COVID-19 Compounds (via MMV COVID Box): Almitrine and Bortezomib Induce Programmed Cell Death in Trypanosoma cruzi." Pathogens 14, no. 2 (2025): 127. https://doi.org/10.3390/pathogens14020127.

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Chagas disease, caused by the protozoan Trypanosoma cruzi, affects millions globally, with limited treatment options available. Current therapies, such as benznidazole and nifurtimox, present challenges, including their toxicity, side effects, and inefficacy in the chronic phase. This study explores the potential of drug repurposing as a strategy to identify new treatments for T. cruzi, focusing on compounds from the Medicines for Malaria Venture (MMV) COVID Box. An initial screening of 160 compounds identified eight with trypanocidal activity, with almitrine and bortezomib showing the highest

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Buckingham, Steven D., Frederick A. Partridge, Beth C. Poulton, et al. "Automated phenotyping of mosquito larvae enables high-throughput screening for novel larvicides and offers potential for smartphone-based detection of larval insecticide resistance." PLOS Neglected Tropical Diseases 15, no. 6 (2021): e0008639. http://dx.doi.org/10.1371/journal.pntd.0008639.

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Pyrethroid-impregnated nets have contributed significantly to halving the burden of malaria but resistance threatens their future efficacy and the pipeline of new insecticides is short. Here we report that an invertebrate automated phenotyping platform (INVAPP), combined with the algorithm Paragon, provides a robust system for measuring larval motility in Anopheles gambiae (and An. coluzzi) as well as Aedes aegypti with the capacity for high-throughput screening for new larvicides. By this means, we reliably quantified both time- and concentration-dependent actions of chemical insecticides fas

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Lucantoni, Leonardo, Sandra Duffy, Sophie H. Adjalley, David A. Fidock, and Vicky M. Avery. "Identification of MMV Malaria Box Inhibitors of Plasmodium falciparum Early-Stage Gametocytes Using a Luciferase-Based High-Throughput Assay." Antimicrobial Agents and Chemotherapy 57, no. 12 (2013): 6050–62. http://dx.doi.org/10.1128/aac.00870-13.

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ABSTRACTThe design of new antimalarial combinations to treatPlasmodium falciparuminfections requires drugs that, in addition to resolving disease symptoms caused by asexual blood stage parasites, can also interrupt transmission to the mosquito vector. Gametocytes, which are essential for transmission, develop as sexual blood stage parasites in the human host over 8 to 12 days and are the most accessible developmental stage for transmission-blocking drugs. Considerable effort is currently being devoted to identifying compounds active against mature gametocytes. However, investigations on the dr

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Kenneth, Obiakor, Chinwuba Obidiegwu Onyeka, Uchechi Ajah Keziah, Chidebe Christian, Henry Ogechi Ajuzie, and Chijioke Uzochukwu Ikemefuna. "Discovery of antiadhesins of Helicobacter pylori from existing drugs and medicines for malaria ventures pathogen box compounds." GSC Biological and Pharmaceutical Sciences 20, no. 3 (2022): 198–212. https://doi.org/10.5281/zenodo.7142478.

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<strong>Background</strong>: <em>Helicobacter pylori</em> infection is a worldwide problem with more than half of the world's population in both developed and developing countries are infected with this organism. The best-characterized <em>H. pylori</em> adhesins, Blood group antigen binding Adhesin (BabA) and Sialic acid binding Adhesin (SabA) are virulent factors which facilitate adhesion of the bacteria to the host cells. <strong>Methods</strong>: We determined the binding affinities of selected existing drugs and medicines for malaria venture pathogen box compounds

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Rice, Christopher A., Emma V. Troth, A. Cassiopeia Russell, and Dennis E. Kyle. "Discovery of Anti-Amoebic Inhibitors from Screening the MMV Pandemic Response Box on Balamuthia mandrillaris, Naegleria fowleri, and Acanthamoeba castellanii." Pathogens 9, no. 6 (2020): 476. http://dx.doi.org/10.3390/pathogens9060476.

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Pathogenic free-living amoebae, Balamuthia mandrillaris, Naegleria fowleri, and several Acanthamoeba species are the etiological agents of severe brain diseases, with case mortality rates > 90%. A number of constraints including misdiagnosis and partially effective treatments lead to these high fatality rates. The unmet medical need is for rapidly acting, highly potent new drugs to reduce these alarming mortality rates. Herein, we report the discovery of new drugs as potential anti-amoebic agents. We used the CellTiter-Glo 2.0 high-throughput screening methods to screen the Medicines for Ma

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Sotorilli, Giuliana Eboli, Humberto Doriguetto Gravina, Ana Carolina de Carvalho, et al. "Phenotypical Screening of an MMV Open Box Library and Identification of Compounds with Antiviral Activity against St. Louis Encephalitis Virus." Viruses 15, no. 12 (2023): 2416. http://dx.doi.org/10.3390/v15122416.

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St. Louis encephalitis virus (SLEV) is a neglected mosquito-borne Flavivirus that may cause severe neurological disease in humans and other animals. There are no specific treatments against SLEV infection or disease approved for human use, and drug repurposing may represent an opportunity to accelerate the development of treatments against SLEV. Here we present a scalable, medium-throughput phenotypic cell culture-based screening assay on Vero CCL81 cells to identify bioactive compounds that could be repurposed against SLEV infection. We screened eighty compounds from the Medicines for Malaria

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Ma, Jingyi, Kimberly Eadie, Marij Schippers, et al. "Novel Compound MMV1804559 from the Global Health Priority Box Exhibits In Vitro and In Vivo Activity against Madurella mycetomatis." International Journal of Molecular Sciences 25, no. 11 (2024): 6227. http://dx.doi.org/10.3390/ijms25116227.

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Objectives: Eumycetoma is a neglected tropical disease (NTD) characterized by subcutaneous lesions and the formation of grains. Attempts to treat eumycetoma involve a combination of antifungal treatment and surgery, although the outcome is frequently disappointing. Therefore, there is a need to identify novel antifungal drugs to treat eumycetoma. In this respect, Medicines for Malaria Venture (MMV) has assembled libraries of compounds for researchers to use in drug discovery research against NTD. Therefore, we screened two MMVOpen compound libraries to identify novel leads for eumycetoma. Meth

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Shanley, Harrison T., Aya C. Taki, Joseph J. Byrne, et al. "A High-Throughput Phenotypic Screen of the ‘Pandemic Response Box’ Identifies a Quinoline Derivative with Significant Anthelmintic Activity." Pharmaceuticals 15, no. 2 (2022): 257. http://dx.doi.org/10.3390/ph15020257.

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Parasitic nematodes cause diseases in livestock animals and major economic losses to the agricultural industry worldwide. Nematodes of the order Strongylida, including Haemonchus contortus, are particularly important. The excessive use of anthelmintic compounds to treat infections and disease has led to widespread resistance to these compounds in nematodes, such that there is a need for new anthelmintics with distinctive mechanisms of action. With a focus on discovering new anthelmintic entities, we screened 400 chemically diverse compounds within the ‘Pandemic Response Box’ (from Medicines fo

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Rollin-Pinheiro, Rodrigo, Mariana Ingrid Dutra da Silva Xisto, Yuri de Castro-Almeida, et al. "Pandemic Response Box® library as a source of antifungal drugs against Scedosporium and Lomentospora species." PLOS ONE 18, no. 2 (2023): e0280964. http://dx.doi.org/10.1371/journal.pone.0280964.

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Scedosporium and Lomentospora species are opportunistic filamentous fungi that cause localized and disseminated infections in immunocompetent and immunocompromised patients. These species are considered resistant fungi due to their low susceptibility to most current antifungal agents used in healthcare settings. The search for new compounds that could work as promising candidate antifungal drugs is an increasing field of interest. In this context, in the present study we screened the Pandemic Response Box® library (Medicines for Malaria Venture [MMV], Switzerland) to identify compounds with an

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dos Santos, Bruna Ramos, Amanda Bruno da Silva Bellini Ramos, Renata Priscila Barros de Menezes, et al. "Repurposing the Medicines for Malaria Venture’s COVID Box to discover potent inhibitors of Toxoplasma gondii, and in vivo efficacy evaluation of almitrine bismesylate (MMV1804175) in chronically infected mice." PLOS ONE 18, no. 7 (2023): e0288335. http://dx.doi.org/10.1371/journal.pone.0288335.

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Toxoplasmosis, caused by the obligate intracellular parasite Toxoplasma gondii, affects about one-third of the world’s population and can cause severe congenital, neurological and ocular issues. Current treatment options are limited, and there are no human vaccines available to prevent transmission. Drug repurposing has been effective in identifying anti-T. gondii drugs. In this study, the screening of the COVID Box, a compilation of 160 compounds provided by the "Medicines for Malaria Venture" organization, was conducted to explore its potential for repurposing drugs to combat toxoplasmosis.

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Rice, Christopher A., Luis Fernando Lares-Jiménez, Fernando Lares-Villa, and Dennis E. Kyle. "In Vitro Screening of the Open-Source Medicines for Malaria Venture Malaria and Pathogen Boxes To Discover Novel Compounds with Activity against Balamuthia mandrillaris." Antimicrobial Agents and Chemotherapy 64, no. 5 (2020). http://dx.doi.org/10.1128/aac.02233-19.

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ABSTRACT Balamuthia mandrillaris is an under-reported, pathogenic free-living amoeba that causes Balamuthia amoebic encephalitis (BAE) and cutaneous skin infections. Although cutaneous infections are not typically lethal, BAE with or without cutaneous involvement is usually fatal. This is due to the lack of drugs that are both efficacious and can cross the blood-brain barrier. We aimed to discover new leads for drug discovery by screening the open-source Medicines for Malaria Venture (MMV) Malaria Box and MMV Pathogen Box, with 800 compounds total. From an initial single point screen at 1 and

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Vallières, Cindy, and Simon V. Avery. "The Candidate Antimalarial Drug MMV665909 Causes Oxygen-Dependent mRNA Mistranslation and Synergizes with Quinoline-Derived Antimalarials." Antimicrobial Agents and Chemotherapy 61, no. 9 (2017). http://dx.doi.org/10.1128/aac.00459-17.

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ABSTRACT To cope with growing resistance to current antimalarials, new drugs with novel modes of action are urgently needed. Molecules targeting protein synthesis appear to be promising candidates. We identified a compound (MMV665909) from the Medicines for Malaria Venture (MMV) Malaria Box of candidate antimalarials that could produce synergistic growth inhibition with the aminoglycoside antibiotic paromomycin, suggesting a possible action of the compound in mRNA mistranslation. This mechanism of action was substantiated with a Saccharomyces cerevisiae model using available reporters of mistr

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Kraft, Thomas E., Monique R. Heitmeier, Marina Putanko, et al. "A novel FRET-based screen in high-throughput format to identify inhibitors of malarial and human glucose transporters." Antimicrobial Agents and Chemotherapy, October 10, 2016, AAC.00218–16. http://dx.doi.org/10.1128/aac.00218-16.

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The glucose transporter PfHT is essential to the survival of the malaria parasitePlasmodium falciparumand has been shown to be a druggable target with high potential for pharmacological intervention. Identification of compounds against novel drug targets is crucial to combating resistance against current therapeutics. Here, we describe the development of a cell-based assay system readily adaptable to high-throughput screening that directly measures compound effects on PfHT-mediated glucose transport. Intracellular glucose concentrations are detected using a genetically encoded fluorescence res

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Tadele, Markos, Solomon M. Abay, Peter Asaga, Eyasu Makonnen, and Asrat Hailu. "In vitro growth inhibitory activity of Medicines for Malaria Venture pathogen box compounds against Leishmania aethiopica." BMC Pharmacology and Toxicology 22, no. 1 (2021). http://dx.doi.org/10.1186/s40360-021-00538-2.

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Abstract Introduction Leishmania aethiopica (L. aethiopica) is responsible for different forms of cutaneous leishmaniasis (CL) in Ethiopia. Treatment heavily depends on limited drugs, together with drawbacks like toxicity and microbial resistance. The current research aimed to investigate in vitro growth inhibitory activity of Medicines for Malaria Ventures - Pathogen Box (MMV - PB) compounds against L. aethiopica clinical isolate. Methodology Four hundred MMV – PB compounds were screened against L. aethiopica using resazurin based colourimetric assay. Compounds with > 70% inhibition were f

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Reader, Janette, Mariëtte E. van der Watt, Dale Taylor, et al. "Multistage and transmission-blocking targeted antimalarials discovered from the open-source MMV Pandemic Response Box." Nature Communications 12, no. 1 (2021). http://dx.doi.org/10.1038/s41467-020-20629-8.

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AbstractChemical matter is needed to target the divergent biology associated with the different life cycle stages of Plasmodium. Here, we report the parallel de novo screening of the Medicines for Malaria Venture (MMV) Pandemic Response Box against Plasmodium asexual and liver stage parasites, stage IV/V gametocytes, gametes, oocysts and as endectocides. Unique chemotypes were identified with both multistage activity or stage-specific activity, including structurally diverse gametocyte-targeted compounds with potent transmission-blocking activity, such as the JmjC inhibitor ML324 and the antit

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Ullah, Imran, Raman Sharma, Antonio Mete, Giancarlo A. Biagini, Dawn M. Wetzel, and Paul D. Horrocks. "The relative rate of kill of the MMV Malaria Box compounds provides links to the mode of antimalarial action and highlights scaffolds of medicinal chemistry interest." Journal of Antimicrobial Chemotherapy, October 29, 2019. http://dx.doi.org/10.1093/jac/dkz443.

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Abstract Objectives Rapid rate-of-kill (RoK) is a key parameter in the target candidate profile 1 (TCP1) for the next-generation antimalarial drugs for uncomplicated malaria, termed Single Encounter Radical Cure and Prophylaxis (SERCaP). TCP1 aims to rapidly eliminate the initial parasite burden, ideally as fast as artesunate, but minimally as fast as chloroquine. Here we explore whether the relative RoK of the Medicine for Malaria Venture (MMV) Malaria Box compounds is linked to their mode of action (MoA) and identify scaffolds of medicinal chemistry interest. Methods We used a bioluminescenc

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Mensah, Eric, P. Bernard Fourie, and Remco P. H. Peters. "Antimicrobial effects of Medicines for Malaria Venture Pathogen Box compounds on strains of Neisseria gonorrhoeae." Antimicrobial Agents and Chemotherapy, October 4, 2023. http://dx.doi.org/10.1128/aac.00348-23.

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ABSTRACT Therapeutic options for Neisseria gonorrhoeae are limited due to emerging global resistance. New agents and treatment options to treat patients with susceptible and multi-extensively drug-resistant N. gonorrhoeae is a high priority. This study used an in vitro approach to explore the antimicrobial potential, as well as synergistic effects of Medicine for Malaria Venture (MMV) Pathogen Box compounds against ATCC and clinical N. gonorrhoeae strains. Microbroth dilution assay was used to determine pathogen-specific minimum inhibitory concentration (MIC) and minimum bactericidal concentra

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Debbert, Stefan L., Mikaela J. Hintz, Christian J. Bell, et al. "Activities of Quinoxaline, Nitroquinoxaline and [1,2,4]Triazolo[4,3-a]quinoxaline Analogs of MMV007204 against Schistosoma mansoni." Antimicrobial Agents and Chemotherapy, November 30, 2020. http://dx.doi.org/10.1128/aac.01370-20.

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The reliance on one drug, praziquantel, to treat the parasitic disease schistosomiasis in millions of people a year shows the need to further develop a pipeline of new drugs to treat this disease. Recently, an antimalarial quinoxaline derivative (MMV007204) from the Medicines for Malaria Venture (MMV) Malaria Box demonstrated promise against Schistosoma mansoni. In this study, 47 synthesized compounds containing quinoxaline moieties were first assayed against the larval stage of this parasite, newly transformed schistosomula (NTS); of these, 16 killed over 70% NTS at 10 μM. Further testing aga

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Vila, Taissa, and Jose L. Lopez-Ribot. "Screening the Pathogen Box for Identification of Candida albicans Biofilm Inhibitors." Antimicrobial Agents and Chemotherapy 61, no. 1 (2016). http://dx.doi.org/10.1128/aac.02006-16.

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ABSTRACT Candida albicans remains the main causative agent of candidiasis, one of the most frequent nosocomial infections, with unacceptably high mortality rates. Biofilm formation is a major risk factor for invasive candidiasis, as Candida biofilms display high-level resistance to most antifungal agents. In this work we have screened the Pathogen Box chemical library (Medicines for Malaria Venture [MMV], Switzerland) in search for inhibitors of C. albicans biofilm formation. Our initial screen identified seven hits, and additional dose-response assays confirmed the biofilm-inhibitory activity

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Tong, Jie Xin, Rajesh Chandramohanadas, and Kevin Shyong-Wei Tan. "High-Content Screening of the Medicines for Malaria Venture Pathogen Box forPlasmodium falciparumDigestive Vacuole-Disrupting Molecules Reveals Valuable Starting Points for Drug Discovery." Antimicrobial Agents and Chemotherapy 62, no. 3 (2018). http://dx.doi.org/10.1128/aac.02031-17.

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ABSTRACTPlasmodium falciparuminfections leading to malaria have severe clinical manifestations and high mortality rates. Chloroquine (CQ), a former mainstay of malaria chemotherapy, has been rendered ineffective due to the emergence of widespread resistance. Recent studies, however, have unveiled a novel mode of action in which low-micromolar levels of CQ permeabilized the parasite's digestive vacuole (DV) membrane, leading to calcium efflux, mitochondrial depolarization, and DNA degradation. These phenotypes implicate the DV as an alternative target of CQ and suggest that DV disruption is an

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Ahyong, Vida, Christine M. Sheridan, Kristoffer E. Leon, Jessica N. Witchley, Jonathan Diep, and Joseph L. DeRisi. "Identification of Plasmodium falciparum specific translation inhibitors from the MMV Malaria Box using a high throughput in vitro translation screen." Malaria Journal 15, no. 1 (2016). http://dx.doi.org/10.1186/s12936-016-1231-8.

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Spalenka, Jérémy, Sandie Escotte-Binet, Ali Bakiri, et al. "Discovery of New Inhibitors of Toxoplasma gondii via the Pathogen Box." Antimicrobial Agents and Chemotherapy 62, no. 2 (2017). http://dx.doi.org/10.1128/aac.01640-17.

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ABSTRACT Toxoplasma gondii is a cosmopolitan protozoan parasite which affects approximately 30% of the population worldwide. The drugs currently used against toxoplasmosis are few in number and show several limitations, such as drug intolerance, poor bioavailability, or drug resistance mechanism developed by the parasite. Thus, it is important to find new compounds able to inhibit parasite invasion or proliferation. In this study, the 400 compounds of the open-access Pathogen Box, provided by the Medicines for Malaria Venture (MMV) foundation, were screened for their anti-Toxoplasma gondii act

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Maccesi, Martina, Pedro H. N. Aguiar, Valérian Pasche, et al. "Multi-center screening of the Pathogen Box collection for schistosomiasis drug discovery." Parasites & Vectors 12, no. 1 (2019). http://dx.doi.org/10.1186/s13071-019-3747-6.

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Abstract Background Over the past five years, as a public service to encourage and accelerate drug discovery for diseases of poverty, the Medicines for Malaria Venture (MMV) has released box sets of 400 compounds named the Malaria, Pathogen and Stasis Boxes. Here, we screened the Pathogen Box against the post-infective larvae (schistosomula) of Schistosoma mansoni using assays particular to the three contributing institutions, namely, the University of California San Diego (UCSD) in the USA, the Swiss Tropical and Public Health Institute (Swiss TPH) in Switzerland, and the Fundação Oswaldo Cru

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Villares, Marie, Nelly Lourenço, Jeremy Berthelet, et al. "Trifloxystrobin blocks the growth of Theileria parasites and is a promising drug to treat Buparvaquone resistance." Communications Biology 5, no. 1 (2022). http://dx.doi.org/10.1038/s42003-022-03981-x.

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AbstractTheileria parasites are responsible for devastating cattle diseases, causing major economic losses across Africa and Asia. Theileria spp. stand apart from other apicomplexa parasites by their ability to transform host leukocytes into immortalized, hyperproliferating, invasive cells that rapidly kill infected animals. The emergence of resistance to the theilericidal drug Buparvaquone raises the need for new anti-Theileria drugs. We developed a microscopy-based screen to reposition drugs from the open-access Medicines for Malaria Venture (MMV) Pathogen Box. We show that Trifloxystrobin (

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Nick, Marina, Frederick A. Partridge, Ruth Forman, et al. "Screening the Medicines for Malaria Venture (MMV) Pandemic Response Box chemical library on Caenorhabditis elegans identifies re-profiled candidate anthelmintic drug leads." Frontiers in Tropical Diseases 3 (October 13, 2022). http://dx.doi.org/10.3389/fitd.2022.1017900.

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The 3 major classes of soil transmitted helminths (whipworm, hookworm and Ascaris) affect 1.5 billion people worldwide mostly in poor countries, where they have adverse effects on child development, nutrition, and the work capacity of adults. Although there are drugs effective on Ascaris, notably the benzimidazoles, those same drugs show poor efficacy particularly against whipworm (Trichuris trichiura) and to a certain extent hookworm. Parasitic nematodes also infect farm livestock and companion animals. Resistance to currently deployed human and veterinary anthelmintic drugs is a growing prob

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Coimbra, Laís D., Alexandre Borin, Marina Fontoura, et al. "Identification of Compounds With Antiviral Activity Against SARS-CoV-2 in the MMV Pathogen Box Using a Phenotypic High-Throughput Screening Assay." Frontiers in Virology 2 (April 14, 2022). http://dx.doi.org/10.3389/fviro.2022.854363.

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Until December 2021, the COVID-19 pandemic has caused more than 5.5 million deaths. Vaccines are being deployed worldwide to mitigate severe disease and death, but continued transmission and the emergence of SARS-CoV-2 variants indicate that specific treatments against COVID-19 are still necessary. We screened 400 compounds from the Medicines for Malaria Venture (MMV) Pathogen Box seeking for molecules with antiviral activity against SARS-CoV-2 by using a high-throughput screening (HTS) infection assay in Vero CCL81 cells. On resupply of 15 selected hit compounds, we confirmed that 7 of them p

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Brahma, Umarani, Siva Singothu, Akash Suresh, et al. "MMV 1804559 is a potential antistaphylococcal and antibiofilm agent targeting the clfA gene of Staphylococcus aureus." Journal of Applied Microbiology, October 29, 2024. http://dx.doi.org/10.1093/jambio/lxae276.

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Abstract Aim Staphylococcus aureus, a high-priority pathogen proclaimed to cause infections ranging from mild to life-threatening, presents significant challenges in treatment. New therapies can be developed quicker using open drug discovery platforms offering a distinct approach to expedite the development of innovative antibacterial and anti-biofilm therapeutics. This study set out to address these issues by finding new uses for current medications to find compounds that are effective against S. aureus. Methods and Results In this study, we screened the global priority health box, launched b

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